Linked Life Data

20392937

Source:http://linkedlifedata.com/resource/pubmed/id/20392937

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2010-4-15
pubmed:abstractText
Glial cell line-derived neurotrophic factor (GDNF) is a neuronal growth factor critical for the development and maintenance of central and peripheral neurons. GDNF is expressed in targets of innervation and provides support to several populations of large, projection neurons. To determine whether GDNF promotes retrograde survival over long axonal distances to cell bodies, we used a compartmentalized culture system. GDNF supported only modest and transient survival of postnatal sympathetic neurons when applied to their distal axons, in contrast to dorsal root ganglion (DRG) sensory neurons in which GDNF promoted survival equally well from either distal axons or cell bodies. Ret, the receptor tyrosine kinase for GDNF, underwent rapid proteasomal degradation in the axons of sympathetic neurons. Interestingly, the level of activated Ret in DRG neurons was sustained in the axons and also appeared in the cell bodies, suggesting that Ret was not degraded in sensory axons and was retrogradely transported. Pharmacologic inhibition of proteasomes only in the distal axons of sympathetic neurons caused an accumulation of activated Ret in both the axons and cell bodies during GDNF stimulation. Furthermore, exposure of the distal axons of sympathetic neurons to both GDNF and proteasome inhibitors, but neither one alone, promoted robust survival, identical to GDNF applied directly to the cell bodies. This differential responsiveness of sympathetic and sensory neurons to target-derived GDNF was attributable to the differential expression and degradation of the Ret9 and Ret51 isoforms. Therefore, the local degradation of Ret in axons dictates whether GDNF family ligands act as retrograde survival factors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5149-58
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:20392937-Animals, pubmed-meshheading:20392937-Axons, pubmed-meshheading:20392937-Biological Transport, Active, pubmed-meshheading:20392937-Cell Culture Techniques, pubmed-meshheading:20392937-Cell Survival, pubmed-meshheading:20392937-Cells, Cultured, pubmed-meshheading:20392937-Ganglia, Spinal, pubmed-meshheading:20392937-Glial Cell Line-Derived Neurotrophic Factor, pubmed-meshheading:20392937-Mice, pubmed-meshheading:20392937-Mice, Inbred BALB C, pubmed-meshheading:20392937-Neurons, pubmed-meshheading:20392937-Proteasome Endopeptidase Complex, pubmed-meshheading:20392937-Protein Isoforms, pubmed-meshheading:20392937-Proto-Oncogene Proteins c-ret, pubmed-meshheading:20392937-Rats, pubmed-meshheading:20392937-Rats, Sprague-Dawley, pubmed-meshheading:20392937-Sensory Receptor Cells, pubmed-meshheading:20392937-Superior Cervical Ganglion, pubmed-meshheading:20392937-Time Factors
pubmed:year
2010
pubmed:articleTitle
The differential axonal degradation of Ret accounts for cell-type-specific function of glial cell line-derived neurotrophic factor as a retrograde survival factor.
pubmed:affiliation
Department of Internal Medicine-Nephrology Division, School of Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural